Protective Effect of Dogwood Alcohol Extract on Hepatic Ischemia Reperfusion Injury based on Network Pharmacology and Transcriptomic Sequencing

Abstract

Background and objective: Hepatic ischemia-reperfusion injury (HIRI) is a key factor leading to complications and poor prognosis after hepatobiliary surgery, but its pathogenesis remains unclear. Hence, it is a very necessary discovery the prevention and treatment methods and pathological mechanism of HIRI. Methods: Our animal experiments indicated that two doses of dogwood alcohol extract (DAX) at 5 g/kg and 2.5 g/kg (crude drug/mouse body mass) could significantly reduce serum alamine aminotransferase (AST) and aspartate aminotransferase (ALT) in HIRI mice. The level of these two transaminases determined the pharmacodynamic effect of DAX on HIRI. Next, we used the results of network pharmacology and transcriptome sequencing to obtain important prevention and cure target genes, and applied molecular docking to simulate receptor and ligand binding. Finally, immunohistochemical method was made use of verifying the results. Results: When the model group vs control group, administration group vs model group, set padj < 0.05, | log2FoldChange | >1.0 filter condition, the intersection between the obtained transcriptome sequencing data set and the network pharmacological target was only heparin-binding epidermal growth factor (HBEGF). Then DockThor online software was applied to make loganin and ursolic acid, small molecular compounds contained in DAX, form complexes with HBEGF active sites through hydrogen bonding to interfere with HIRI. Meanwhile, immunohistochemical test results showed that HBEGF expression decreased in the administration group compared with the model group ( *P < 0.05 ). Conclusions: DAX interferes with the occurrence and development of HIRI by down-regulating HBEGF. Our experimental results not only highlight the advantages of traditional Chinese medicine in treating difficult diseases, but also provide a reference for clinical exploration of new methods to prevent and treat HIRI.